tbuckley/cabot-search huggingface dataset:
Implementation of a rapid access multidisciplinary pathway to reduce health disparities in veterans with thoracic malignancies.
Authors: Sabrina Wilcox, Kate Taylor, Melisa Besko, Mina Pirzadeh
Journal: Journal of Clinical Oncology (2023)

e18583 Background: Lung cancer has higher incidence and lower survival rates in Veterans compared to the general population. Previous investigation at our institution identified delays in care for veterans with new lung cancer diagnoses often due to patient factors including transportation, lodging, or too many appointments. Modifiable factors we aimed to improve included coordination and consolidation of care related to diagnostic work-up. We implemented a rapid access pathway (RAP), including a multidisciplinary panel of providers who review outside referrals for imaging concerning for thoracic malignancy with a goal of identifying appropriate invasive diagnostic work-up prior to initial consultation visit. Patients eligible had an initial telehealth visit and were offered a two-day consolidated diagnostic visit, with lodging. Methods: Retrospective chart review was conducted on veterans referred to the Veterans Affair Ann Arbor Healthcare System for lung cancer work-up and who were eligible for RAP from 10/2021- 12/2022. Data abstracted included veteran demographics, comorbidities, indication for initial imaging, tumor stage, and treatment rendered. Time intervals between abnormal image to multidisciplinary conference (T0), conference to telehealth consult (T1), telehealth consult to tissue diagnosis (T2), tissue diagnosis to treatment (T3), total time from abnormal image to treatment (T4) were calculated. Incidence and type of system delay (SD) versus patient delay (PD) was recorded with each care interval. Results: 306 new consults underwent multidisciplinary review; 20 were eligible for the RAP; 4 declined a consolidated visit. Sixteen Veterans at least partially completed the pathway by the time of analysis. 93% (n = 15) were male, 81% (n = 13) identified as White. Median age at referral was 74 and median Charleston-Comorbidity Index was 5, with 62% having mobility issues. 56% lived at least 50 miles from the Ann Arbor VA. Disease was detected by lung cancer screening in 56%, incidental finding in 37%, and symptom triggered in 6%. Median times to each interval were T0 13.5 days, T1 5.5 days, T2 28 days, T3 34 days and T4 70 days. SD was observed in 11% of patients; most commonly due to administrative scheduling changes. PD occurred in 35% of patients, often prior to diagnostic procedure or treatment initiation; most commonly due to a new hospitalization, patient wanting more time prior to treatment or declining work-up/treatment. Conclusions: Our aim was to expedite diagnosis and treatment of new potential lung cancers in Veterans by mitigating barriers commonly experienced in the healthcare system without compromising quality of care. All veterans who participated in all stages of the RAP received RAND guideline concordant care (time from abnormal image to treatment initiation &lt; 98 days). Ongoing analysis will include clinical outcomes following RAP implementation.
Clinical assessment of HRD scoring in relation to PARPi response in terms of statistical guidance on reporting results for CDx tests evaluation.
Authors: Atil Bisgin, Ibrahim Boga, Kaan Ihsan Eskut, Cagla Rencuzogullari, Ozge Sonmezler, Fatih Kose, Ali Ayberk Besen, Omer Fatih Olmez, Umut Disel, Nazım Emrah Kocer, Filiz Bolat, Dan-Corneliu Jinga, Ioana Lazar, Surajit Pathak
Journal: Journal of Clinical Oncology (2023)

e17597 Background: Homologous recombination deficiency (HRD) is a tumor characteristic that can be assessed via different biomarkers such as individual mutations in BRCA1 and BRCA2 genes, and/or other HRR genes and genomic instability. We assessed a combined HRD score in three measures; BRCAs mutations, HRR mutation (HRRm) status, and genomic instability scoring via a specific bioinformatic algorithm of the testing panel to establish clinical validation. Methods: We tested 157 ovarian cancer patients’ FFPE samples to define HRD score, BRCA1/2 mutation and other HRRm status, to camper the responses to PARP inhibitors. For the HRD scoring, all the samples that were previously tested with alternative HRD tests and the cases had an indication of PARPi also tested via HRDInfo (CE-IVD) Panel for clinical diagnostics in this study. The PPA, NPA and OPA have been measured according to the FDA regulations of overall agreement for a follow-on CDx to show clinical evidence. Results: Depending on the three levels of testing strategy, BRCA1-2 mutation status in relation to the clinical response for PARPi has the lowest positive percent agreement (PPA) with 63.41% while HRD score has the highest with 97.62% that is higher than the any alternative HRD tests. All the PPA, NPA and OPA measures showed in the Figure for BRCA1-2 status and Genomic Instability stand alone and all BRCA1-2 plus other HRR genes plus Genomic Instability Status (GIS) to define HRD scoring. Conclusions: Even though the testing rate of HRD tests are still low all around the world and limited to specific cancers, there is an increasing requirement for different types of cancers. However, most alternative HRD tests have high overall concordance but fail to reach FDA CDx test requirements. Thus, this study showing the clinical evidence in the treatment of PARPi response data together with high PPA, NPA and OPA measures of HRDInfo panel and its bioinformatics algorithm. [Table: see text]
Clinical and molecular characteristics of patients with AML with an exceptional response to ivosidenib.
Authors: Justin M. Watts, Prapti Arvind Patel, Sung Choe, Xiaofei Bai, Dylan M. Marchione, Eytan M. Stein
Journal: Journal of Clinical Oncology (2023)

7036 Background: Ivosidenib (IVO) twas approved based on a CR/CRh rate of 31.8% in IDH1 mutant (IDH1m) R/R AML; median duration of CR/CRh (DOR) was 8.2 months (mo). The purpose of this study is to elucidate the clinical and molecular characteristics of exceptional responders to single agent IVO. Methods: We analyzed all patients (pts) with IDH1m R/R AML who received IVO 500mg QD on the phase 1 dose escalation/expansion study and had a DOR of &gt;12 mo. Results: Of 179 pts who received IVO 500 mg QD, 57 (31.8%) achieved a CR/CRh. Of these, 20 (35.1%) had a DOR &gt;12 mo. After excluding 7 pts who went to HSCT, 13 (22.8% of responders, 7.3% of cohort) had DOR &gt;12 mo (exceptional response) and 8 (14% of responders, 4.5% of cohort) had DOR &gt;24 mo. The 13 exceptional responders all achieved CR as best response, and median DOR was 42.6 mo. Median OS was not reached; estimated OS at 48 mo was 67.1%. Median EFS was 44.4 mo. Reasons for discontinuing treatment included relapse (n=4), adverse event unrelated to IVO (n=3), and patient (pt) decision (n=3). Three pts remain on treatment. All pts who relapsed had DOR between 1-2 years; none of the 8 pts with DOR &gt;2 years relapsed. Baseline characteristics are in the table. The most common co-mutations were DNMT3A, ASXL1, SRSF2, and JAK2 (3 each, 23%). Five pts (39%) had a splicing factor mutation. No pts had FLT3 or RTK pathway mutations other than JAK2. Only 1 pt with NPM1 had an exceptional response, and 1 pt had TP53 (VAF 3.6%). Six pts (46%) had an abnormal karyotype, 6 normal (46%), and 1 missing (8%). Most pts had intermediate-risk cytogenetics (10 pts, 77%), 2 poor-risk, and 1 missing. The median IDH1 VAF was 25% (range 10-50%). The median number of co-mutations was 1 (range 0-6). Having 0-1 co-mutations was associated with a longer response. Eleven pts (85%) had an IDH1 R132C mutation; 1 each (7.7%) had R132H and R132L mutations. Mutation clearance of IDH1 was noted in 8 pts (61.5%). Conclusions: A subset of pts with IDH1m R/R AML have prolonged CR on single agent IVO without HSCT (22.8% of CR/CRh responders) and no pts in CR for &gt;2 years (14% of CR/CRh responders) relapsed. A low mutational burden, lack of RTK pathway mutations and canonical AML drivers, and co-occurrence of mutations associated with clonal hematopoiesis appear to be associated with exceptional response. Clinical trial information: NCT02074839 . [Table: see text]
Training and validation of a model predicting clusters of long-term cancer-related behavioral symptoms (CRBS) after breast cancer (BC).
Authors: Martina Pagliuca, Julie Havas, Florence Lerebours, Olivier Rigal, Thierry Petit, Sylvie Giacchetti, Florence Dalenc, Johanna Wassermann, Olivier Arsene, Anne-Laure Martin, Sibille Everhard, Ines Maria Vaz Duarte Luis, Antonio Di Meglio
Journal: Journal of Clinical Oncology (2023)

12087 Background: Fatigue, cognitive impairment, emotional distress, and sleep disturbance are prevalent and challenging symptoms among patients (pts) with BC. These symptoms often tend to cluster, they are usually responsive to similar behavioral interventions (e.g., exercise, psychosocial), and can be collectively defined as CRBS. We aimed to generate a model to predict clusters of long-term CRBS. Methods: CANcer TOxicity (CANTO; NCT01993498) is a prospective cohort of pts with stage I-III BC collecting longitudinal data at diagnosis (dx) and yearly post-dx. Our outcome was the proportion of pts reporting a cluster of ≥3 severe CRBS (EORTC QLQ-C30/HADS) 4 years post-dx. Clinical, behavioral, treatment (tx)-related predictors, and the baseline Behavioral Symptoms Score (BSS; based on the number of severe CRBS as proxy of symptom burden at dx) were tested in a training cohort (Mar 2012 - Feb 2015) with a multivariable logistic regression model implementing bootstrapped Augmented Backwards Elimination and 10-fold internal cross-validation. Performance was externally validated in pts from a subsequent enrolment period (Mar 2015 - Apr 2018). Results: In the training cohort (N=3555), 92.1% of pts had stage I-II BC, 52.6% received chemo, and 81.9% endocrine tx. At dx, 22.0% pts had severe fatigue (C30≥40/100), 29.7% severe cognitive impairment (C30&lt;75/100), 33.9% and 6.5% clinically suggestive anxiety and depression (HADS≥11/21), respectively, and 35.2% severe insomnia (C30&gt;50/100). 19.0% of pts reported a severe CRBS cluster at dx, then 21.0% did so 4 years post-dx. Younger age, previous psychiatric disorders, and higher baseline BSS were predictors of CRBS clusters (Table;AUC 0.73 [95%CI 0.71-0.75]). Results were confirmed in the validation cohort (N=1533). Conclusions: 1 in 5 pts reports a cluster of severe CRBS 4 years post-dx of BC. Younger pts with previous psychiatric disturbance and a higher symptom burden at dx have greater risk of long-term CRBS. Systematic clinical implementation of predictive tools at dx of BC can aid a more thorough screening and referrals to targeted behavioral interventions. Clinical trial information: NCT01993498 . [Table: see text]
Demographic and socioeconomic factors of patients with nonencapsulated sclerosing carcinoma: An NCDB analysis.
Authors: Laura Stewart, Xinxin Wu, Darby Keirns, Peter T. Silberstein, Beau Hsia
Journal: Journal of Clinical Oncology (2023)

e18103 Background: Nonencapsulated sclerosing carcinoma (NSC) is a rare and aggressive variant of papillary thyroid carcinoma (PTC) that accounts for 0.7-6.6% of its cases. It is associated with greater rates of vascular invasion, metastasis, and relapse compared to classic PTC. With prompt initiation of aggressive treatment including radical surgery, lymph node resection, and possible radioiodine treatment, NSC has a 10-year survival rate of 93%. Given the importance of proper diagnosis and selection of aggressive treatments, data regarding its epidemiology could further improve patient outcomes. The demographics of NSC patients were analyzed using the National Cancer Database (NCBD). Methods: Data from NCDB was queried and patients with a confirmed diagnosis of NSC between 2004 and 2020 were identified for a retrospective cohort analysis (N = 1,130). Yearly diagnosis rates were analyzed using regression analysis. Factors including patient age, sex, race, insurance status, urban/rural residence, surgical treatment approach, treatment facility type, and 90-day mortality were identified and evaluated via descriptive statistics. Results: The NCDB contained a total of 1,130 patients with a confirmed diagnosis of NSC from 2004 – 2020. The incidence rate of new diagnoses remained stable over this time (R2 = 0.0). Women were much more likely to be diagnosed (78.5%) compared to men (21.5%) with an average age at diagnosis of 44.0 years (SD = 18.7, range = 6 – 90 years). Most patients were White (86.0%), lived in metropolitan areas with a greater than 1 million population (56.5%), and were privately insured (68.9%). The vast majority of patients were treated surgically (99.9%). A complete thyroidectomy was the most common surgical approach (89.3%), more so than subtotal thyroidectomy or lobectomy. For the patients with valid data, the most common treatment facility type was an academic/research program (42.6%) followed by comprehensive community cancer programs (33.8%). Most patients survived at least ninety days after their primary surgery (98.2%) and were still alive at the date of last contact (88.4%). Conclusions: NSC is an aggressive subtype of PTC, but it generally has a good prognosis with initiation of aggressive treatment. The findings of this research corroborated previous studies showing that NSC is much more common in females than males, is most commonly treated with complete thyroidectomy, and has high 90-day survival rates. In examining the demographic features of this patient population, it was found that the majority of patients were White, lived in large metropolitan areas, and were privately insured. This may suggest that a relative ease of access to healthcare aided in their diagnosis. Future research should focus on understanding how demographic and socioeconomic factors may contribute to the timing of diagnosis, chosen treatments, and overall mortality rates of patients with NSC.
Spatial profiling of ovarian clear cell carcinoma (OCCC) and identification of immune-hot features.
Authors: Ya-Ting Tai, Wei-Chou Lin, Duncan Yi-Te Wang, Jieru Ye, Tuan Zea Tan, Lin-Hung Wei, Ruby Yun-Ju Huang
Journal: Journal of Clinical Oncology (2023)

e17543 Background: OCCC is an ovarian cancer subtype with high incidence in Asia. Despite its frequent occurrence as an early-stage disease, optimal therapeutic options for high-risk patients are limited. Recently, immune-hot features have been proposed as an indicator for poor prognosis for early-stage OCCC. Specific patterns of intra-tumoral heterogeneity (ITH) associated with these immune-hot features have yet to be defined. Methods: Formalin-fixed paraffine embedded (FFPE) tumor sections from 10 early-stage primary OCCC patients were included. Digital Spatial Profiling (DSP) of 18 protein targets from the Human Protein Core Panel was conducted by using the nanoString GeoMx system to profile selected regions of interest (ROIs) based on the reference H&amp;E staining morphology. Areas of illumination (AOIs) were defined according to ROI segmentation by the fluorescence signals of pan-cytokeratin (PanCK), CD45, or DNA. The digital signals were quantified by the nanoString nCounter system. Results: Unsupervised hierarchical clustering of 252 AOIs from 229 ROIs showed 5 distinct clusters. PanCK+ AOIs distributed in 5 clusters were found to express combinations of markers suggestive of immune mimicry: granzyme B (GZMB) high epithelial cells (C1-a), immune signal high epithelial cells (C1-b), immune-like cells (C1-c), fibronectin-high epithelial cells (C2-a), and signal-cold epithelial cells (C2-b). CD45+ AOIs were mostly clustered in C1-c. Tumor cells with C1-c and C2-a features were associated with recurrence while those in C1-a were associated with no recurrence (Chi-square p=2.8E-04). Tumor infiltrating immune cells (TIIs), which were found to be more enriched of the macrophage lineage (stronger CD68 expression, p=4.5E-03), were associated with recurrence (66.7% in recurrence vs 14.3% in no recurrence, Chi-Square p=0.098). TIIs appeared in PanCK segments of C1-b and C1-c with higher frequencies (45% in C1-b, 25% in C1-c, Chi-square p=0.046) and in PanCK segments of C1-a with extremely low frequency (0%). Correlating with morphology, tumors with recurrence showed higher frequency of papillary pattern (54.7%, Chi-Square p=1.01E-04) and lower frequency of tubulocystic pattern (18.9%, Chi-Square p=7.21E-03). Plus, TIIs were found with high frequency in ROIs with papillary pattern (65.2%, Chi-Square p=4.99E-04) and low frequency in ROIs with tubulocystic pattern (8.7%, Chi-Square p=6.43E-03). Papillary ROIs, which showed macrophage lineage immune mimicry, high CD68 intensity and low PanCK intensity, were found to have very low frequency of PanCK segments of C1-a (6.2%, Chi-Square p=1.26E-04), but extremely high frequency (100%) of PanCK segments of C1-c. Conclusions: Spatial profiling of early-stage OCCC tumors revealed immune-hot tumor features associated with recurrence. These features included immune mimicry of tumor cells, the presence of TIIs, and a papillary pattern in morphology.
Advanced cervical cancer therapy: Comparison of contemporary expert and healthcare professional recommendations from an online treatment decision tool.
Authors: Lauren S. Prescott, Jerfiz Constanzo, Ritu Salani, Renata R. Urban, Shannon Neville Westin, Timothy A. Quill, Linda R. Duska
Journal: Journal of Clinical Oncology (2023)

5528 Background: Practice patterns for the management of advanced cervical cancer are rapidly evolving given the emergence of novel treatment options. We developed an online Interactive Decision Support Tool (IDST) for advanced cervical cancer to provide expert guidance to healthcare professionals (HCPs). Methods: With input from 5 experts, an IDST was developed for patient scenarios with newly diagnosed (ND) and recurrent/second-line (2L) advanced cervical cancer. The IDST included expert insights on 352 scenarios based on criteria such as adenopathy, disseminated disease status, previous therapy, and actionable biomarkers (PD-L1, MMR/MSI, TMB). Users were asked to enter specific patient criteria and their intended management approach. The IDST then showed the 5 expert recommendations for that specific scenario and HCPs were asked to indicate whether the recommendations changed their intended treatment plan. Expert recommendations vs user-selected therapy for different scenarios were analyzed. We present self-reported practice patterns in this disease setting and the impact of expert recommendations on treatment choice. Results: At this interim analysis, 141 unique learners used the IDST, entering 232 unique patient scenarios. Data from the IDST also showed areas of consensus and controversy in treating patients with advanced cervical cancer. For locally advanced, ND, no adenopathy and no metastases, all experts recommended pelvic chemoradiation with or without brachytherapy vs only 61% of HCPs; 16% and 3% of those entering cases for the locally advanced ND setting indicated expert recommendation changed their treatment choice and that barriers impeded the recommendations, respectively. For advanced ND, with adenopathy, metastatic, PD-L1–positive cervical cancers, all experts vs 50% of HCPs chose an immunotherapy-containing platinum-based chemotherapy regimen with/without bevacizumab; 9% of those indicated barriers to implementing expert recommendations. In 2L recurrent disease, all experts chose either single-agent immunotherapy (if PD-L1 positive) or tisotumab vedotin (if PD-L1 negative) vs 45% and 40% of HCPs, respectively; 19% of those selecting 2L therapy in the recurrent setting said the expert recommendations had changed their intended choice. Conclusions: Analysis from this IDST indicates differences in practice patterns between experts and HCPs for various case scenarios of advanced cervical cancer. Online decision support tools may increase the number of HCPs making optimal treatment decisions for advanced cervical cancer, particularly when new data, indications, and guideline updates must be considered. Updated and detailed analyses from the IDST will be presented.
Comparative proteomic profiling of plasma exosomes in patients with lung cancer with brain metastasis and liver metastasis.
Authors: Sini Li, Yan Qu, Lihui Liu, Hua Bai, Jie Wang
Journal: Journal of Clinical Oncology (2023)

e21123 Background: Brain or liver metastases are the main causes of lung cancer-related death. Predicting liver or brain metastases before having evidence from imaging of the tumors is challenging, but important for early patient intervention. Accumulating evidence has suggested that circulating exosomes in the blood could mediate cancer metastasis by transferring specific proteins to the target cells. Methods: Using liquid chromatography-MS/MS, we analyzed the proteomic profiles of plasma exosomes derived from 42 metastatic lung cancer patients (including 26 solitary brain metastasis (BM) and 16 solitary liver metastasis (LM)), 25 local advanced (LA) lung cancer patients without metastasis, and 5 healthy controls (HC), and explored organ-specific proteomic biomarkers. Results: 120 and 143 differentially expressed exosomal proteins were found to be the dysregulated candidates in BM and LM of lung cancer (BM-DEEPs, LM-DEEPs), as compared to the LA lung cancer samples, respectively. The bioinformatics analyses indicated the homogeneity and heterogeneity in BM-DEEPs and LM-DEEPs. In terms of homogeneity, they were mainly involved in the protein activation cascade, collagen-containing extracellular matrix, and ECM-receptor interaction. In terms of heterogeneity, the BM-DEEPs were significantly enriched in S100 protein and calcium-dependent protein, while the LM-DEEPs were mainly enriched in integrin, lipoprotein, heat shock protein and proteoglycans. Moreover, our study also revealed the heterogeneity in plasma-derived exosome proteomics in patients with non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC), which partly explained the different metastatic characteristics of NSCLC and SCLC. Additionally, we found that MUC5B and SELL could be used as a reliable diagnostic marker of BM, while APOH, CD81 and CCT5 could help to diagnose LM in lung cancer patients. Conclusions: For the first time, we revealed the comprehensive and comparative proteomic profiles of plasma-derived exosomes from lung cancer patients with solitary brain and liver metastasis. We further proposed some potential biomarkers and pathological mechanisms, which could serve as excellent resource for further studies investigating lung cancer metastasis.